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TitleDe novo identification of mammalian ciliary motility proteins using cryo-EM.
Journal, issue, pagesCell, Vol. 184, Issue 23, Page 5791-5806.e19, Year 2021
Publish dateNov 11, 2021
AuthorsMiao Gui / Hannah Farley / Priyanka Anujan / Jacob R Anderson / Dale W Maxwell / Jonathan B Whitchurch / J Josephine Botsch / Tao Qiu / Shimi Meleppattu / Sandeep K Singh / Qi Zhang / James Thompson / Jane S Lucas / Colin D Bingle / Dominic P Norris / Sudipto Roy / Alan Brown /
PubMed AbstractDynein-decorated doublet microtubules (DMTs) are critical components of the oscillatory molecular machine of cilia, the axoneme, and have luminal surfaces patterned periodically by microtubule inner ...Dynein-decorated doublet microtubules (DMTs) are critical components of the oscillatory molecular machine of cilia, the axoneme, and have luminal surfaces patterned periodically by microtubule inner proteins (MIPs). Here we present an atomic model of the 48-nm repeat of a mammalian DMT, derived from a cryoelectron microscopy (cryo-EM) map of the complex isolated from bovine respiratory cilia. The structure uncovers principles of doublet microtubule organization and features specific to vertebrate cilia, including previously unknown MIPs, a luminal bundle of tektin filaments, and a pentameric dynein-docking complex. We identify a mechanism for bridging 48- to 24-nm periodicity across the microtubule wall and show that loss of the proteins involved causes defective ciliary motility and laterality abnormalities in zebrafish and mice. Our structure identifies candidate genes for diagnosis of ciliopathies and provides a framework to understand their functions in driving ciliary motility.
External linksCell / PubMed:34715025 / PubMed Central
MethodsEM (single particle)
Resolution3.4 - 8.0 Å
Structure data

EMDB-24663:
Cryo-EM density map of the outer dynein arm core from bovine tracheal cilia
Method: EM (single particle) / Resolution: 8.0 Å

24664

7rro

EMDB-24664: Composite cryo-EM density map of the 48-nm repeat doublet microtubule from bovine tracheal cilia
PDB-7rro: Structure of the 48-nm repeat doublet microtubule from bovine tracheal cilia
Method: EM (single particle) / Resolution: 3.4 Å

Chemicals

ChemComp-GTP:
GUANOSINE-5'-TRIPHOSPHATE / GTP, energy-carrying molecule*YM

ChemComp-MG:
Unknown entry

ChemComp-GDP:
GUANOSINE-5'-DIPHOSPHATE / GDP, energy-carrying molecule*YM

Source
  • bos taurus (cattle)
KeywordsSTRUCTURAL PROTEIN / cilia / microtubule / dynein / motility

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